基因CDH11编码钙黏着蛋白-11,一种II型钙黏着蛋白超家族成员,其含有5个细胞外钙黏着蛋白(EC)结构域。钙粘蛋白-11通过EC1结构域进行反式二聚化以产生钙粘蛋白复合物。在Elsahy-Waters综合征(EWS)中观察到复合杂合和纯合功能丧失CDH11变体,显示了典型的颅面特征,椎体异常,2-3个数字的皮肤并打印,泌尿生殖系统异常,智力残疾。杂合CDH11变体可导致Teebi过度端粒综合征(THS),以眼睛和尿道下裂为特征。我们报告了一名THS患者,该患者具有涉及EC1结构域的新型CDH11变体。患者是一名10个月大的男性,发育里程碑正常,但是眼睛间隔很宽,斜视,尿道下裂,披肩阴囊,大拇指(X射线右双拇指),左四指多指,左侧第三/第四手指的皮肤联合。外显子组测序鉴定了从头杂合CDH11变体(NM_001797.4:c.229C>T[p。Leu77Phe]NC_000016.9:g.64998856G>A)。临床特征与先前报道的THS患者一致,但是多义,大拇指,EWS的皮肤分型特征与皮肤分型重叠。THS和EWS可能代表CDH11相关疾病的谱。这种新型CDH11变体中的残基Leu77为一个大的疏水口袋,其中伴侣钙粘蛋白11的侧链插入以反式二聚化,表明cadherin-11结构可能在该变体中被改变。
The gene CDH11 encodes cadherin-11, a Type II cadherin superfamily member that contains five extracellular cadherin (EC) domains. Cadherin-11 undergoes trans-dimerization via the EC1 domain to generate cadherin complexes. Compound heterozygous and homozygous loss-of-function CDH11 variants are observed in Elsahy-Waters syndrome (EWS), which shows characteristic craniofacial features, vertebral abnormalities, cutaneous syndactyly in 2-3 digits, genitourinary anomalies, and intellectual disability. Heterozygous CDH11 variants can cause Teebi hypertelorism syndrome (THS), which features widely spaced eyes and hypospadias. We report a THS patient with a novel CDH11 variant involving the EC1 domain. The patient was a 10-month-old male with normal developmental milestones, but had widely spaced eyes, strabismus, hypospadias, shawl scrotum, broad thumbs (right bifid thumb in x-ray),
polysyndactyly of the left fourth finger, and cutaneous syndactyly of left third/fourth fingers. Exome sequencing identified a de novo heterozygous CDH11 variant (NM_001797.4:c.229C > T [p.Leu77Phe] NC_000016.9:g.64998856G > A). Clinical features were consistent with previously reported THS patients, but
polysyndactyly, broad thumb, and cutaneous syndactyly overlapped phenotypic features of EWS. THS and EWS may represent a spectrum of CDH11-related disorders. Residue Leu77 in this novel CDH11 variant lines a large hydrophobic pocket where side chains of the partner cadherin-11 insert to trans-dimerize, suggesting that the cadherin-11 structure might be altered in this variant.